FDA approves Truvada for PrEP
At this year’s conference we heard about exciting advances in cure research, as well as the launch of the International AIDS Society’s (IAS) “Towards an HIV Cure” global scientific strategy. A two-day pre-conference workshop brought together researchers and community advocates to preview some of these advances and provide insight into work being done in the seven different areas of research that the agenda has identified as highest priority.
The workshop, co-chaired by Steven Deeks, MD, University of California, San Francisco, and IAS president and Nobel laureate Françoise Barré-Sinoussi, Pasteur Institute, Paris, was opened by Dr. Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases, NIH. In his opening remarks, Fauci stated that a cure that only benefits 0.01% of the population is not going to excite anyone—it has to be scalable.
During the community literacy session Australian researcher Sharon Lewin, MD, PhD, gave an overview presentation addressing major barriers to a cure, including what actually defines a cure and potential targets and mechanisms, as well as underscoring the importance of assays for future research and the need for these tests to undergo rigorous standardization with labs before going into wider use.
Activist and POSITIVELY AWARE contributor Matt Sharp talked about his experiences as a cure research study participant, and the challenges that lie ahead, including ethical study design, Analytical Treatment Interruptions (ATI), and informed consent.
Sharp noted that some cure research may be quite risky, with little chance for benefit. He asked what the “reasonable” risks are for HIV-positive individuals who will be participating in early and potentially dangerous cure studies, and how can we best protect them? Developing guidelines for determining when potentially risky treatment interruptions are appropriate is a critical next step, said Sharp, and community input and community advisory boards are essential in ensuring ethical, patient-oriented studies.
An elegant presentation given by Robert Siliciano, MD, PhD, Johns Hopkins University School of Medicine, was perhaps one of the clearest and most concise presentations I’ve ever seen on the basics of immunology, HIV infection, and the multiple molecular mechanisms which maintain HIV latency. HIV is not completely eradicated from the body by standard antiretroviral therapy because some of it lies resting in memory CD4+T-cells, which can proliferate for an average of 73.4 years in the human body. However, if you stop taking therapy, the virus typically comes roaring back within a matter of weeks. One eradication approach would be to remain on standard ARV therapy to keep the virus suppressed, while at the same time purging these latent reservoirs and blocking them from infecting new cells, so that they would have nowhere to go and eventually die off, ridding the body of HIV. But it’s complicated—the number of latently infected cells may be much higher than previously thought, by as much as 50-fold, according to Siliciano.
Sarah Palmer, PhD, Swedish Institute for Communicable Disease Control and Karolinska Institute, gave a presentation on measuring persistent HIV infection, including an excellent slide outlining some of the advantages and disadvantages of the four currently available assays which measure persistence. In concluding her talk, Palmer emphasized that “looking ahead, to determine the effectiveness of curative strategies, our field will need to develop a more standardized assay system which is sensitive, efficient, less costly, and adaptable in local settings.”
Other presentations covered recent advances in the development of accurate animal models for use in future cure research, vaccine and immune-based therapies and the role of immune activation and inflammation in viral persistence.
The conference ended with a slightly unorthodox, yet immensely informative and entertaining presentation by Fred Verdult of Amsterdam on the psychosocial benefits of a cure for HIV. Verdult, after finding out he had HIV in 1998, started Volle Maan, an organization that conducts studies and communication projects on health and disease to encourage people to live full and worthwhile lives. Volle conducted a survey of 458 individuals in the Netherlands asking how important to them a cure for HIV is, why a cure is important, and which type of cure is preferred.
The majority of the survey respondents indicated they were in good health, with only 14% stating that their health was poor. Seventy-two percent said that it was very important to them to be cured of HIV, while another 22% said it was somewhat important. Yet when asked about how a cure might look, participants had varying responses. 95% thought that a total cure without any risk of future transmission or infection very desirable, while only 41% considered it desirable to have a cure that had no risk of future transmission but carried a risk of future infection. The survey also asked about disadvantages of living with HIV—the risk of experiencing health problems in the future was the number one answer, while psychosocial effects such as stigma and the risk of infecting someone else were also highly ranked.
Deeks closed the two-day workshop by declaring Verdult’s presentation the “highlight of the meeting,” and remarking on the spirit of collaboration among the attendees. Barré-Sinoussi said that next steps include the efforts of the working groups, including a newly added social sciences research team and an ethics working group, as well as a call for more cure research funding and collaboration. The next IAS Towards an HIV Cure workshop is scheduled for immediately prior to the 2013 international conference in Kuala Lumpur, Malaysia.
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HIV prevention pill recommended
A group of patients in France who became infected with HIV and then started on antiretroviral therapy (ART) early in the post-infection period have shown no signs of a resurgence of their HIV infection seven years after being taken off therapy.
“These results suggest that…antiretroviral treatment should be started very early after infection,” said Charline Bacchus, lead researcher of the study at the French National Agency for Research on AIDS and Viral Hepatitis (ANRS).
The patients in the ANRS EP47 VISCONTI cohort (known as the Visconti Cohort) have an extremely low reservoir of HIV in their cells similar to that of “HIV controller” patients. HIV controllers are those who are able to control their HIV infection without the use of ART for an extended period of time, and represent about one out of every 300 people who have HIV.
In the study, 12 patients started therapy within 10 weeks of infection, were on therapy for an average of three years, and were able to control HIV after an average of seven years off therapy. At a press conference Asier Saez-Cirión, one of the study investigators, said they were interested in finding out whether HIV controller status could be induced. He estimated that 5–15% of those treated early could eventually control HIV off therapy. But don’t stop those HIV meds just yet—not only would we need to figure out how to identify who would have this type of response to early treatment, but also get those individuals onto treatment immediately following infection. The other question one might ask is, could some of those in the study already have been HIV controllers to begin with? While the genetic alleles commonly associated with HIV controllers was not found in these patients there may be other factors playing a role, which researchers now are trying to uncover.
Another study looked at two men who had been infected with HIV for many years, on suppressive antiretroviral therapy (ART), and who underwent treatment of lymphoma via an allogenic (meaning foreign, or from another donor) stem cell transplantation. Both patients received a milder form of chemotherapy, known as the conditioning regimen, prior to transplant, which allowed them to stay on their ART during and after the transplant. One patient was on Atripla, the other on Isentress/Truvada. HIV was detectable in their cells immediately after the transplant, but the transplanted donor cells replaced the patients’ own lymphocytes over time. The amount of HIV DNA in their blood cells decreased and became undetectable, for up to two years now in one patient and three-and-a-half years in the other. CD4s declined in both patients initially, followed by a robust CD4 increase in one patient, and the stabilization and no further decline of CD4s in the other.
Unlike Timothy Ray Brown, the “Berlin” patient, who received cells that were resistant to HIV because they lacked the CCR5 receptor, these patients received cells that were CCR5+. It is believed that the antiretroviral treatment protected the donor cells from becoming infected, leading one researcher to refer to it as “a form of PrEP [pre-exposure prophylaxis] at the cellular level.” Further tissue sampling and analytic treatment interruption will need to be conducted to assess the full extent of the reduction of HIV in the reservoir.
At a press conference held the same day these two studies were presented, David Margolis, MD, University of North Carolina at Chapel Hill, was asked by a reporter about the media’s role in reporting on cure advances responsibly and accurately, while at the same time not giving too much hope or creating complacency.
“That’s your job,” said Margolis. “We are very careful about what we say [as researchers], and we’ve defined cure several different ways. Different kinds of cure and eradication mean different things to different people, and have different levels of value. Perhaps we should come up with a word, like ‘complicated-eradication-chemo-immunotherapy,’ to slow people down. But you can’t argue with the goal and you can’t get there without working on it—and I can’t say how long it will take.”
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Another home HIV test
Complera, the newest single tablet regimen (STR), comprised of rilpivirine (Edurant) plus emtricitabine/tenofovir (Truvada), continues to hold its own. Previously, it had been shown to be non-inferior to Atripla, another STR, made of efavirenz (Sustiva) plus emtricitabine/tenofovir. This time, however, it has been shown to maintain an undetectable viral load (of less than 50 copies/mL) in people who were switching from a Norvir-boosted protease inhibitor (PI) combination.
These were 24-week results in nearly 500 individuals, of whom two-thirds were switched to Complera and the rest maintained on their PI regimen. Overall total cholesterol, LDL (“bad cholesterol”), and triglycerides decreased to a greater extent among those switched than on those maintained on their PI. The differences were statistically significant.
“We all know that regimen simplification improves quality of life,” said Frank Palella, MD, of Northwestern University when he presented these results from the SPIRIT study.
Also continuing to do well: the still investigational elvitegravir and dolutegravir, both integrase inhibitor medications (INSTIs). In 96-week results from Study 145, elvitegravir continued to be non-inferior (as it was in earlier 48-week results) to Isentress, the only INSTI currently on the market. Development of INSTI drug resistance was low (about 7%) and similar with both medications. The 700 participants in this study were treatment-experienced, so they were less likely to achieve undetectable viral load. Overall, 47.6% of the 351 participants on dolutegravir had undetectable viral loads, compared to 45% of those on Isentress.
In 48-week results from the SPRING-2 study, dolutegravir was as effective as Isentress, with 88% vs. 85% of participants in the two groups achieving undetectable viral load. The participants were treatment-naïve (first time on HIV therapy), See more dolutegravir news in Briefly.
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The investigational drug cobicistat (COBI), which boosts drug levels (a “pharmacoenhancer”), was given with Reyataz plus Truvada and compared to Norvir-boosted Reyataz plus Truvada, a preferred regimen under U.S. treatment guidelines. In Phase 3 study results after 48 weeks, cobicistat-boosted Reyataz was non-inferior to Norvir-boosted Reyataz, with high rates of virologic success (viral loads of less than 50 copies per mL) and similar safety and tolerability. Nearly 700 individuals participated in Study 114.
“Cobicistat appears to be an effective drug for boosting protease inhibitor levels, with greater potential for co-formulation,” said presenter Joel Gallant, MD, MPH of Johns Hopkins University School of Medicine. He noted the various co-formulations of cobicistat with protease inhibitors that are in development. Moreover, he pointed out that, “[Norvir]-boosted Reyataz is known to be a lipid-friendly regimen and cobicistat is no different.”
“This is all good news,” said session co-facilitator Christine Katlama, MD, of Hospitalier Pitie-Salpetriere in Paris, “because all the drugs work and when they don’t work there is no resistance.”
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HIV prevention pill recommended
Several sessions looked at abuses that put sex workers at risk for HIV—and we’re not talking sex.
Instead, it’s police actions around the world—including here in the United States—to confiscate condoms and to use them as evidence of prostitution that puts sex workers at risk for HIV. Advocates said the situation is such that many sex workers are afraid to carry condoms because of the police harassment this can cause. In fact, even outreach workers have been followed by the police so that sex workers can be arrested when they take the condoms offered. As advocates pointed out, it is not illegal to carry condoms. Rather, confiscation serves as another avenue of illegal detention and intimidation.
Moreover, criminalization of consensual sex work keeps workers under dangerous conditions. In the “Criminalizing Condoms and Sex Work” session, Acasia Shields, author of Criminalizing Condoms, a report from the Open Society Foundation, said, “Police routinely search sex workers to confiscate and destroy condoms. This affects their ability to practice safe sex and they know it.”
Of the U.S. sex workers surveyed, 52% said they were afraid to carry condoms because of fear of police harassment. Shields said other abuses include threats of arrest to exhort sex, and beating or raping sex workers.
Discussing the findings from the first national congress of sex workers in Bangladesh, Simon Risen, MD, MPH, PhD, of Save the Children, said, “Violence against female sex workers spreads far beyond individual incidents and factually is gender-based violence.” Among other recommendations, Save the Children in Bangladesh says behavioral change campaigns should be aimed at changing community perceptions and creating acceptance of sex workers in mainstream society, and that maternal and child services should focus more on issues related to sex workers.
Darby Hickey of the Los Angeles chapter of SWOP (Sex Workers Outreach Project), said, “We think sometimes that countries like the United States are a world apart from countries like Bangladesh, but unfortunately, we face the same issues. It is about law and about policy change, but also about how police operate outside the range of law. So we need to change policies, holding police accountable, and address the wider societal indifference and downright hostility.” She said efforts to “rescue and save” sex workers should be called “arrest and abuse.”
In the session titled “The Oldest Profession: Is Sex Work Work?,” Naomi Akers said equating sex work with human trafficking is insulting and hurts both sex workers, who are targeted by raids, and victims of trafficking, who aren’t helped at all. “When you’re doing sex work, of course you see it as work. It buys you food and helps you take care of your family,” she said, calling trafficking “horrible.”
Deanna Kerrigan of the Johns Hopkins Bloomberg School of Public Health in Baltimore detailed findings of higher HIV risk among sex workers around the world, and said support for sex workers’ groups, as well as human and health rights is critical for all sex workers, including men and transgender people. Labor rights, the focus of the session, would help to eliminate stigma and discrimination and increase HIV prevention efforts for this group of workers, she said. Richard Howard of the International Labour Office (ILO) said, “Decent work [as outlined by ILO] should exist for all human beings, regardless of whether it’s legal or not, whether it takes place in a formal or informal environment.”
Underscoring the human rights issues affecting sex workers were protests against the U.S. Consulate for denying them visas to attend the conference.
In the final analysis, the sex workers movement advocates for decriminalization of sex work as the most important way of protecting their human rights.
“The epidemic is not driven by the lack of a pill or a gadget, the epidemic is driven by repression,” said plenary speaker Cheryl Overs, Senior Research Fellow at the Michael Kirby Centre for Public Health and Human Rights at Monash University in Melbourne.
She founded a sex workers’ rights organization in Australia in the ‘80s and the Global Network of Sex Work Projects in the ‘90s. She has worked in HIV policy and programming for male, female, and transgender sex workers in more than 20 developing countries. “And that brings me to law and policy,” she continued. “Sex workers from Sweden to Singapore to Swaziland all say that the greatest threat to their health and human rights is the law that makes it impossible to find safe places to work, and prevents them from having the same protections as other workers and other citizens.”
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Another home HIV test
With an annual budget approaching $31 billion, the National Institutes of Health (NIH) is the medical research agency of the federal government and the largest source of funding in the world for medical research. The NIH is also a driving force behind AIDS and HIV vaccine research; 10% of the agency’s budget—$3 billion—goes toward HIV/AIDS, funding research conducted at academic, commercial, and private labs, as well as at NIH headquarters in Bethesda, Maryland.
Some 75 buildings are scattered throughout the 312-acre NIH campus. During the International AIDS Conference, the agency hosted a press tour of two of those buildings, offering a closer look at the role the NIH plays in clinical research and treatment.
Opened in 2000, the Vaccine Research Center is a five-story facility where research is done to find vaccines not only for HIV, but for influenza, Ebola virus, and other diseases that pose global health risks.
Gary J. Nabel, MD, PhD, director of the Vaccine Research Center, opened the tour, explaining how the facility serves as an “intellectual hub” by putting all the stages of vaccine research and development under one roof.
Basic research is first conducted to find a promising vaccine candidate. A vaccine is of little use, however, if it can’t be efficiently and safely mass-produced, so it undergoes test production for good manufacturing practices and quality control. From there, a successful candidate then goes to clinical trials to determine how safe it is for patient use. Results from the trials are reviewed in a series of assessments. If the vaccine candidate doesn’t pass this process with flying colors, it goes back to basic research, and the cycle begins again. The three-phase cycle can take 10–18 years for a would-be
vaccine to complete.
Nabel said that the search for a vaccine has been elusive, because, “HIV is constantly mutating, changing its genetic make-up and protein structure.”
“HIV is a sugar-coated virus,” Nabel explained. Sugars produced by the body are converted into proteins by the virus. “This makes it invisible to the body’s immune system, which does not perceive the virus as a threat.”
However, Nabel offered some perspective on the search for an HIV vaccine. Although it took 17 years to develop a vaccine against hepatitis B, he pointed out that a polio vaccine took 45 years.
“A vaccine is at least 10 years into our future,” Nabel said. “What we’ve learned is that HIV is a very crafty virus.”
While one or two vaccine candidates look promising, it will be at least until mid-2013 before an assessment can be made, and a little longer to evaluate more mature data, Nabel said. Even if a vaccine were discovered today, it would take at least four years of additional testing and evaluation before it could become publicly available.
Next stop on the tour was the Mark O. Hatfield Clinical Research Center, a hospital where 1,500 clinical trials for a variety of illnesses (including HIV/AIDS) are conducted. Opened in 2005, the Hatfield Clinical Research Center is connected to the Warren Grant Magnuson Clinical Center, built in 1953, to form the largest hospital in the U.S. dedicated to clinical research.
The Clinical Research Center has spawned numerous treatments, from the first pediatric chemotherapy to development of AZT, the first anti-HIV drug. The center houses an HIV clinic that treats 500 patients, only one or two of whom are ever in-patients.
Dr. Henry Masur is the research center’s Director of Critical Care Medicine, but has focused the major part of his career on HIV and its associated complications. Although a research institution, Masur said the clinic recognizes the importance of keeping HIV-positive patients connected to care. That’s why while half the clinic’s nursing staff is in research, the other half of the nurses are also case managers.
Hepatitis C is a major concern for people who are HIV-positive, Masur said. There are 3–5 million people who have hep C out of 314 million Americans. While the current standard of care for hepatitis C can sometimes be difficult to tolerate and only helps to clear the virus in about one-third to one-half of patients, recent advances have raised the cure rate to 75% and higher. Masur said advances in treatment look even more promising, comparing them to the advent of protease inhibitors and combination therapy for HIV that came in 1995.
As people are now living longer with HIV, Masur said the research center is beginning to look at aging and other complications. “We’ll soon be examining neurocognitive issues,” he said. “Beyond anecdotally, does it happen, and if so, what can we do to reverse it?”
“Knowledge is bi-directional,” Masur said. “What we learn in the lab will help patients. But there is a lot we can learn from patients and put to use.”
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Scene's from a week that was
Beyond the headline-making sessions of the International AIDS Conference, there was much to see and do inside and away from Washington, D.C.’s convention center. “What would an AIDS conference be without a little protesting?” said an unflappable Secretary of State Hilary Clinton as a small group of demonstrators rose and chanted when she took the stage on opening day.
During a panel discussion addressing the efficiency of overseas anti-AIDS efforts, Bill Gates spoke candidly: “The amount of money we have [now] is not enough to treat everyone. We’re in a period of incredible uncertainty about how much this funding will stay strong. Even the uncertainty creates instability in how the investment ahead will be made. The voices of the AIDS community are going to have to be louder than ever.”
The week of the conference offered opportunities to honor the fallen and plea for the living. Visitors to the AIDS Memorial Quilt, displayed on the Mall, could not only see the panels, but also recite the names of those memorialized by the Quilt.
In the streets, approximately 1,000 marchers took their messages to the White House. Discordant voices—demonstrating for sex workers’ rights, against Wall Street, opposing HIV criminalization laws—were united by one refrain, “cure AIDS now.”
